A Potential Role for the NOD1 Variant (rs6958571) in Gram-Positive Blood Stream Infection in ELBW Infants

Venkatesh Sampath; Neil Mulrooney; Aloka L Patel; Jonathan Cohen; Liyun Zhang; Jeffery Garland; Pascal M Lavoie; John Dagle; Pippa Simpson

doi:10.1159/000477433

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A Potential Role for the NOD1 Variant (rs6958571) in Gram-Positive Blood Stream Infection in ELBW Infants

Journal article

Peer reviewed

A Potential Role for the NOD1 Variant (rs6958571) in Gram-Positive Blood Stream Infection in ELBW Infants

Venkatesh Sampath, Neil Mulrooney, Aloka L Patel, Jonathan Cohen, Liyun Zhang, Jeffery Garland, Pascal M Lavoie, John Dagle and Pippa Simpson

Neonatology (Basel, Switzerland), Vol.112(4), pp.354-358

2017

DOI: 10.1159/000477433

PMID: 28768269

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Abstract

The genetic basis of sepsis susceptibility in preterm infants remains understudied. Herein, we investigated the nucleotide binding-oligomerization domain (NOD)-like receptor (NLR) family of immune receptors as putative loci for preterm sepsis susceptibility. To determine whether single nucleotide polymorphisms (SNPs) in NLR genes are associated with blood stream infections (BSI) in premature infants. An international cohort of infants with gestational age (GA) <35 weeks were genotyped for SNPs in the ATG16L1, CARD8, NLRP3, NOD2, and NOD1 genes. χ2 and logistic regression analyses were used to examine relationships between NLR variants and BSI. Among 764 infants, 138 developed BSI, 113 had gram-positive bacterial (GPB) BSI, and 28 had gram-negative bacterial (GNB) BSI. Infants with BSI had a lower birth weight and GA (p < 0.001), but did not differ in gender, race, or chorioamnionitis. NLR variants were not associated with GPB or GNB BSI in the entire cohort. The CC genotype of the NOD1 SNP (rs6958571) was associated with increased GPB BSI in extremely low birth weight (ELBW, birth weight <1,000 g) infants (OR = 3.3, 95% CI: 1.4-7.5, p = 0.003, n = 362) and in Caucasian infants (OR = 2.5, 95% CI: 1.2-5.4, p = 0.016, n = 535). Regression models adjusting for clinical variables identified ELBW status and the NOD1 CC genotype as risk factors for GPB BSI in Caucasian infants. In this study investigating relationships between NLR variants and sepsis in infants with GA <35 weeks, the NOD1 (rs6958571) SNP was associated with GPB BSI in Caucasian infants and ELBW infants. Replication of our results in an independent cohort would support a role for NLR variants in determining sepsis risk in ELBW infants.

Phenotype

Bacteremia - blood

Bacteremia - diagnosis

Bacteremia - epidemiology

Bacteremia - genetics

Birth Weight

Chi-Square Distribution

European Continental Ancestry Group - genetics

Female

Gene Frequency

Genetic Predisposition to Disease

Gestational Age

Gram-Positive Bacterial Infections - blood

Gram-Positive Bacterial Infections - diagnosis

Gram-Positive Bacterial Infections - epidemiology

Gram-Positive Bacterial Infections - genetics

Humans

Infant, Extremely Low Birth Weight

Infant, Newborn

Infant, Premature

Logistic Models

Male

Nod1 Signaling Adaptor Protein - genetics

Odds Ratio

Polymorphism, Single Nucleotide

Risk Factors

Details

Title: Subtitle: A Potential Role for the NOD1 Variant (rs6958571) in Gram-Positive Blood Stream Infection in ELBW Infants
Creators: Venkatesh Sampath - Children's Mercy Hospital
Neil Mulrooney
Aloka L Patel
Jonathan Cohen
Liyun Zhang
Jeffery Garland
Pascal M Lavoie
John Dagle
Pippa Simpson
Resource Type: Journal article
Publication Details: Neonatology (Basel, Switzerland), Vol.112(4), pp.354-358
DOI: 10.1159/000477433
PMID: 28768269
ISSN: 1661-7800
eISSN: 1661-7819
Language: English
Date published: 2017
Academic Unit: Stead Family Department of Pediatrics; Epidemiology; Biochemistry and Molecular Biology; Neonatology
Record Identifier: 9984293081702771

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